TABLE 1

Evidence-based recommendations for the use of each of the six tests considered for primary ciliary dyskinesia (PCD) diagnosis

Which patients should be referred for diagnostic testing?
Based on moderate confidence in the evidence:

  1. We recommend that patients are tested for PCD if they have several of the following features: persistent wet cough; situs anomalies; congenital cardiac defects; persistent rhinitis; chronic middle ear disease with or without hearing loss; a history in term infants of neonatal upper and lower respiratory symptoms or neonatal intensive care admittance (strong recommendation)

  2. Patients with normal situs presenting with other symptoms suggestive of PCD (as listed in recommendation 1) should be referred for diagnostic testing (strong recommendation)

  3. Siblings of patients should be tested for PCD, particularly if they have symptoms suggestive of PCD (as listed in recommendation 1) (strong recommendation)

  4. We recommend the use of combinations of distinct PCD symptoms and predictive tools (e.g. PICADAR) to identify patients for diagnostic testing (weak recommendation)

In patients suspected of having PCD should nasal nitric oxide be used as a diagnostic tool?
Based on moderate confidence in the evidence, we recommend that:

  1. Nasal nitric oxide measurement should be used as part of the diagnostic work-up of school children aged >6 years and adults suspected of having PCD, preferably using a chemiluminescence analyser with a velum closure technique (strong recommendation)

  2. In children aged <6 years suspected of having PCD, we suggest nasal nitric oxide measurement using tidal breathing as part of the diagnostic work-up (weak recommendation)

    Remark: we suggest that patients presenting with a strong clinical history should undergo further testing, even if nasal nitric oxide is normal (weak recommendation)

In patients suspected of having PCD should HSVA be used as a diagnostic tool?
Based on low confidence in the evidence, we recommend:

  1. HSVA, including ciliary beat frequency and beat pattern analysis, should be used as part of the diagnostic work-up of patients suspected of having PCD (weak recommendation)

  2. Ciliary beat frequency should not be used without assessment of ciliary beat pattern in diagnosing PCD (strong recommendation)

  3. To improve diagnostic accuracy of HSVA, CBF/P assessment should be repeated after ALI culture (strong recommendation)

In patients suspected of having PCD should TEM be used as a diagnostic tool?
Based on low confidence in the evidence, we recommend:

  1. Ciliary ultrastructure analysis by TEM should be used as part of the diagnostic work-up of patients suspected of having PCD (strong recommendation)

  2. Further diagnostic investigations should be performed in patients with normal ultrastructure if the clinical history is strong (strong recommendation)#

  3. In patients with hallmark ciliary ultrastructure defects for PCD further confirmatory diagnostic investigations are not required (strong recommendation)

In patients suspected of having PCD, should genotyping be used as a diagnostic tool?
There were no studies that fulfilled inclusion criteria to answer this question. Statements to assist the clinician are made in the genetics sections but these are not evidence based. Therefore, we could not make formal recommendations as for other diagnostic procedures. However, we have provided a list of Task Force statements on genetics, which is based upon agreement between experts rather than published evidence.
In patients suspected of having PCD, should immunofluorescence be used as a diagnostic tool?
There were no studies that fulfilled inclusion criteria to answer this question. Statements to assist the clinician are made in the immunofluorescence sections but these are not evidence based. Therefore, we could not make formal recommendations as for other diagnostic procedures. However, we have provided a list of Task Force statements on immunofluorescence, based upon agreement between experts rather than published evidence.

  • TEM: transmission electron microscopy; HSVA: high-speed video microscopy analysis. #: normal ciliary ultrastructure, as resolvable by TEM, does not exclude the diagnosis of PCD (16% PCD-positive patients have TEM without a detectable defect); : patients with hallmark ciliary ultrastructure defects for PCD (absence of outer dynein arms, combined absence of inner and outer dynein arms, inner dynein arm absence combined with microtubular disarrangement) assessed by TEM almost always have PCD (false-positive results are very rare ≈0.7%). CBF/P: ciliary beat frequency/pattern; ALI: air–liquid interface.